Infectious Disease Serology

Hepatitis B Serology

No single immunology pattern is tested more than the hepatitis B virus (HBV) panel. Learn what each marker means and you can read any combination.

Interpretation logic:

• HBsAg+, IgM anti-HBc+: acute hepatitis B.
• HBsAg+ for >6 months, IgG anti-HBc+, HBsAg persists: chronic hepatitis B.
• Anti-HBs+, anti-HBc+ (HBsAg-): resolved past infection with immunity.
• Anti-HBs+ only (anti-HBc negative): vaccine-induced immunity — the cleanest exam discriminator, because vaccine contains only surface antigen, never core.
• Anti-HBc+ alone (HBsAg-, anti-HBs-): the window period (HBsAg has cleared, anti-HBs not yet detectable) or a remote/occult infection.

Worked example: A healthy nurse tests anti-HBs positive but anti-HBc negative and HBsAg negative. Because the core antibody is absent, this is vaccine-induced immunity, not past natural infection.

Syphilis Serology

Syphilis (Treponema pallidum) testing pairs two test types because each has a distinct role.

• Non-treponemal tests — RPR and VDRL: detect reagin (antibody to cardiolipin). They are inexpensive screens, give a quantitative titer that falls with treatment, and are used to monitor therapy. They can give biologic false positives in pregnancy, lupus, mononucleosis, and other conditions.
• Treponemal tests — FTA-ABS, TP-PA, EIA: detect specific antibody to the organism, confirm a reactive screen, and usually remain reactive for life even after cure (so they cannot monitor treatment).

The traditional algorithm screens with RPR/VDRL, then confirms positives with a treponemal test. The reverse algorithm screens with a treponemal EIA first, then reflexes to RPR. A fourfold drop in RPR titer after treatment (e.g., 1:32 → 1:8) indicates adequate response.

HIV Testing

The current CDC-recommended algorithm is a fourth-generation antigen/antibody combination immunoassay that detects both p24 antigen and HIV-1/HIV-2 antibodies, shortening the diagnostic window. A reactive screen is confirmed by an HIV-1/HIV-2 antibody differentiation immunoassay; indeterminate results reflex to a nucleic acid (RNA) test. The older Western blot confirmation has been replaced by this differentiation assay.

Other Tested Serologies And Titers

• Mononucleosis (EBV): heterophile antibody (Monospot); confirmed by EBV-specific antibodies (VCA IgM = acute, EBNA = past).
• Streptococcal: anti-streptolysin O (ASO) titer rises after group A strep infection (post-strep glomerulonephritis, rheumatic fever).
• Rubella / TORCH: IgM = acute or congenital; IgG = immunity.

Titer rule: report the highest dilution still showing reactivity. A fourfold rise (two doubling dilutions, e.g., 1:16 → 1:64) between acute and convalescent specimens is the standard evidence of recent infection.

High-Yield Traps

• Vaccine gives anti-HBs only; natural infection adds anti-HBc.
• Treponemal tests stay positive for life — use the non-treponemal titer to follow treatment, never the treponemal test.
• The HBV window period is detected by IgM anti-HBc when both HBsAg and anti-HBs are negative.
• A single high titer is less meaningful than a rising titer across paired sera.

Hepatitis A And C

Beyond hepatitis B, the exam expects basic interpretation of the other hepatitis viruses. Hepatitis A virus (HAV) is spread fecal-orally and causes acute, self-limited disease: IgM anti-HAV indicates acute infection, while IgG anti-HAV indicates past infection or vaccination and lifelong immunity. Hepatitis C virus (HCV) is blood-borne and frequently chronic; screening detects anti-HCV antibody by immunoassay, but because antibody cannot distinguish active from resolved infection, a reactive screen is confirmed by HCV RNA (nucleic acid) testing to prove active viremia.

This antibody-then-RNA logic mirrors the HIV algorithm and reinforces the rule that antibody alone does not prove active disease.

TORCH And Congenital Infections

The TORCH panel screens for congenital infections: Toxoplasma, Other (syphilis, varicella, parvovirus B19), Rubella, Cytomegalovirus, and Herpes simplex. The interpretive key is the immunoglobulin class:

• IgG in a newborn may be maternal (transferred across the placenta) and does not by itself prove neonatal infection.
• IgM in a newborn indicates true congenital infection, because IgM does not cross the placenta.

Reading Serology In Clinical Context

Serologic interpretation is the highest-yield application skill in this domain. A practical decision sequence:

1. Identify the antibody class present — IgM suggests acute, IgG suggests past or immune.
2. Decide whether antigen or nucleic acid testing is needed to prove active disease (HBsAg, p24, HCV RNA).
3. For paired sera, look for a fourfold rise before calling acute infection.
4. Reconcile the result with the clinical picture; if they conflict, consider technical artifacts.

Worked example: A blood donor screens reactive for anti-HCV. Because antibody persists after both active and resolved infection, the laboratory reflexes to HCV RNA: a positive RNA confirms current infection, while a negative RNA suggests cleared or resolved disease. Reporting active hepatitis C from the antibody screen alone would be an interpretive error.

Additional Traps

• HAV/HCV: IgM anti-HAV = acute HAV; anti-HCV reactive needs HCV RNA confirmation.
• A newborn's IgG can be maternal; only IgM proves congenital infection.
• HIV uses a fourth-generation antigen/antibody screen, then a differentiation immunoassay, not Western blot.